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Biomedical subjects

T David

Publications and source records attributed to T David.

At least 19 recordsLinked to original sources

Corneal wound healing modulation using basic fibroblast growth factor after excimer laser photorefractive keratectomy.

Photorefractive keratectomy with the 193-nm excimer laser is one of the most promising innovations in refractive surgery. However, routine clinical application is hindered by two main obstacles, i.e., postoperative subepithelial opacity and possible regression of the refractive result. Because we have previously demonstrated beneficial effects of basic fibroblast growth factor (bFGF) on corneal epithelial healing in different in vivo models, we investigated the influence on both epithelial and stromal healing of topical bFGF after excimer laser keratomileusis in a rabbit model. After 7-mm circular deepithelialization, the eyes of 24 New Zealand White rabbits received identical deep stromal laser ablations (depth 50 microns, 6 D, diameter 5 mm) and were randomly assigned to one of four treatment groups [control (phosphate-buffered saline, PBS), bFGF 10 micrograms/application, dexamethasone 0.1%, bFGF + dexamethasone, n = 12 eyes/group]. All treatments were administered four times daily--bFGF until complete epithelial healing, dexamethasone and PBS until 3 months postsurgery. Wound surface regression on time was determined by means of computer-assisted image analysis of fluorescein-stained corneas. Corneal opacity was observed biomicroscopically and graded using a previously established scoring system. After bFGF application for 2-3 days only, a highly significant acceleration in epithelial wound healing speed was found compared with the rate of the other three treatment groups (p < 0.001). A combined therapy (bFGF + steroid) had no effect on the healing rate. Compared with control values, mean scores for subepithelial haze in the other groups were found to be nearly 50% lower during the first 2 postoperative months.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Defining potential targets for immunotherapy in Burkholderia cepacia infection.

Burkholderia cepacia has become a serious source of infection in patients with cystic fibrosis. Antibiotic therapy is difficult as the bacteria are intrinsically resistant to most antibiotics. The present study compared the antibody response by immunoblot of 50 negative control sera, 22 patients with cystic fibrosis and no evidence of B. cepacia, 9 clinically well patients with cystic fibrosis colonised by B. cepacia and 5 patients with cystic fibrosis and deteriorating or fatal B. cepacia infection. Nineteen antigenic bands varying in apparent molecular weights from 19 to 170 kDa were identified. Two bands at 19 and 21 kDa were only present when the organism was grown in an iron-deficient medium. The band at 30 kDa was identified as a porin and the possession of IgG antibody carried a statistically significant (P = 0.00003) better prognosis. This antigen was thus a potential target for immunotherapy.

Antibodies, Bacterial

Determination of the curvatures and bending strains in open trileaflet heart valves.

The leaflets of trileaflet artificial heart valves manufactured from polyurethane, gluteraldehyde-treated porcine aortic valves and pericardial tissue are subject to cyclic stresses and strains which can reduce the lifetime of the implanted valves through leaflet calcification and fatigue failure. A detailed knowledge of the stress state within a valve leaflet throughout a cardiac cycle is desirable in order to improve the geometry of the valve leaflets and ultimately improve the valve performance. An experimental method to evaluate the radius of curvature at the free edge of the open valve leaflet is presented. The technique has been applied to polyurethane trileaflet heart valves manufactured within the authors' laboratory and to commercially available bioprosthetic valves in the fully open position under steady and pulsatile flow conditions. Simple bending theory has been applied to the polyurethane valves to calculate bending stresses and strains at the free leaflet edge based on the measured curvature. The results showed that in the fully open position the highest curvatures occurred at the commissural regions for all the valves analysed. Additional areas of high curvature were present along the free leaflet edge. Average curvatures as high as 0.85 mm-1 were observed at the leaflet commissures for the polyurethane valves with a resultant bending stress of 0.72 MPa. The porcine bioprosthetic valves showed average curvatures as high as 2.5 mm-1 which also occurred at the leaflet commissures. The results of the study have been compared to values of stress obtained from numerical analysis of closed polyurethane valve leaflets reported in the literature.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Cytotoxic effects of FGF2-saporin on bovine epithelial lens cells in vitro.

PURPOSE: To test the ability of two preparations of FGF2-saporin, either FGF2 chemically conjugated to saporin (FGF2-SAP) or genetically engineered FGF2-saporin (rFGF2-SAP) to inhibit the growth of bovine epithelial lens (BEL) cells in vitro when in solution and when immobilized on heparin surface-modified (HSM) polymethylmethacrylate (PMMA) intraocular lenses (IOLs). METHOD: Bovine epithelial lens cells were incubated with various concentrations FGF2-saporin for as long as 4 days. The number of surviving cells was determined by counting the number of nuclei. Because FGF2 binds to heparin, FGF2-saporin was incubated with HSM PMMA IOLs; excess toxin was washed off, and the BEL cells were grown on the FGF2-saporin-treated IOLs (HSM and non-HSM) for 4 days. Cell density was determined by image analysis. RESULTS: Both FGF2-SAP and rFGF2-SAP were highly cytotoxic (nM range), with rFGF2-SAP 10 times less active than FGF2-SAP. FGF2-saporin bound to the surface of HSM IOLs and eluted by 2M NaCl retained its activity. Toxin bound to HSM IOLs killed more than 90% of the BEL cells placed on the IOL surface within 4 days. The ability of FGF2-saporin to prevent the growth of cells on the IOL surface was strictly dependent on the presence of heparin on the IOL. CONCLUSIONS: FGF2-saporin is bound to HSM PMMA IOLs and prevents the growth of epithelial cells on the surface of the lens.

Animals

In vivo inhibition of lens regrowth by fibroblast growth factor 2-saporin.

PURPOSE: To investigate the ability of fibroblast growth factor (FGF) 2-saporin to prevent lens regrowth in the rabbit. METHODS: Chemically conjugated and genetically fused FGF2-saporin (made in Escherichia coli) were used. Extracapsular extraction of the lens was performed on the rabbit, and the cytotoxin either was injected directly into the capsule bag or was administered by FGF2-saporin-coated, heparin surface-modified (HSM) polymethylmethacrylate intraocular lenses. The potential of the conjugate was checked by slit lamp evaluation of capsular opacification and by measuring crystallin synthesis. Toxin diffusion and sites of toxin binding were assessed by immunohistochemistry. Possible toxicity was determined by histologic analysis of ocular tissues. RESULTS: FGF2-saporin effectively inhibited lens regrowth when it was injected directly into the capsular bag. However, high concentration of the toxin induced transient corneal edema and loss of pigment in the iris. Intraocular lenses coated with FGF2-saporin reduced lens regrowth and crystallin synthesis without any detectable clinical side effect. After implantation, FGF2-saporin was shown to have bound to the capsules and, to a lesser extent, to the iris; no histologic damage was found on ocular tissues as a result of implantation of drug-loaded HSM intraocular lenses. CONCLUSIONS: Chemically conjugated (FGF2-SAP) and genetically fused FGF2-saporin (rFGF2-SAP) bound to HSM intraocular lenses can prevent lens regrowth in the rabbit.

Animals

[The clinical course of surgically managed para-articular femoral fractures in geriatric surgery].

246 patients (average 82.4 years) with proximal femur fractures treated with bipolar endoprosthesis, sliding lag screw or Ender nailing, related to the fracture type were analysed in a retrospective study. Pre-existing diseases, duration of operation, postoperative complications, transfusions, hospital stay, mobility achieved and mortality were noted. In result we found a high multimorbidity related to the age, the highest requirement of transfusions in patients undergoing Ender nailing, a long period to achieve postoperative mobility, a long hospital stay and increasing mortality with average age and average hospital stay.

Aged

A new method to evaluate cardiovascular response in anesthetized rats. Hypertension after variable intensity, brief electrical stimuli.

To establish and standardize a nociceptive response in anesthetized rats, the hypertensive responses to defined electrical and mechanical stimuli were studied. Rats (n = 7) were given etomidate, 3.8 mg/kg/hr intravenously (i.v.) 2 hr following carotid artery and jugular vein cannulation. At 15 min after beginning the infusion, four types of noxious stimuli were administered sequentially at 1-min intervals (14 stimuli total): Type 1: Square electrical waves, 125 cps, 1.6 msec, 2-sec train duration, varying current from 0.4 to 12 mA (11 stimuli); Type 2: A single 10-mA electrical stimulus, 5-sec train duration; Type 3: Tail clamping; and, Type 4: Skin incision. After each stimulus, maximum change in systolic blood pressure (delta SBP) was measured. delta SBP after the most intense stimuli was as follows: Type 1 (12 mA, 2 sec), 32.1 +/- 2.14 mmHg; Type 2 (10 mA 5 sec), 42.9 +/- 2.4 mmHg; Type 3 (tail-clamping), 34.3 +/- 3.3 mmHg; Type 4 (skin incision), 14.2 +/- 2.8 mmHg. For the multiple Type-2 stimuli, a relationship between current and delta SBP was present. The authors believe that characterized graded electrical stimulation will allow a more quantitative evaluation of the hypertensive response to noxious stimuli in etomidate anesthetized rats, as compared to observing a single response to a single stimulus. The characterization of the electrical stimulation by amplitude, frequency, and wave form makes research work on nociception under anesthesia easily reproducible.

Anesthesia

Preliminary experience with the Toronto SPV stentless porcine bioprosthesis for aortic valve replacement.

From November 1992 to March 1993 fourteen patients received the Toronto SPV stentless porcine xenograft as aortic valve replacement. Median age was 56 years (range 32-70 years). 7 patients were male and 7 female. Implanted valve sizes ranged from 23 mm to 29 mm, the majority of patients received valves with 27 and 29 mm tissue diameter. A learning process was evident by aortic crossclamp time decreasing with experience. No valve-related mortality or morbidity occurred. Postoperatively echocardiography showed near normal valve performance in most patients. The longevity of the valve, however, still has to be established. Meanwhile we continue the implant of stentless bioprostheses as aortic valve substitutes in selected patients.

Adult

Basic fibroblast growth factor modulates corneal wound healing after excimer laser keratomileusis in rabbits.

We have previously demonstrated beneficial effects of basic fibroblast growth factor (bFGF) on corneal epithelial healing in different in vivo models. In the present study, we investigated the influence on epithelial and stromal healing of topical bFGF after excimer laser keratomileusis in a rabbit model. The corneas of 24 New Zealand white rabbits were deepithelialized (7-mm diameter) and subsequently received identical deep stromal laser ablations (depth, 50 microns; 6 D; diameter, 5 mm). The animals were randomly assigned to one of four treatment groups: PBS (control); bFGF at 500 ng/application; dexamethasone 0.1%, and bFGF+dexamethasone (n = 12 eyes/group). All treatments were given four times daily; with bFGF being given until complete epithelial healing and dexamethasone and PBS, until 3 months postsurgery. Wound surface regression on time was determined by means of computer-assisted image analysis of fluorescein-stained corneas. Corneal opacity was scored using slit-lamp observation and graded following a previously established scoring system. As compared with the other three treatment groups, a highly significant acceleration in the rate of epithelial wound healing was found after bFGF application for 2-3 days only (P < 0.001). A combined therapy (bFGF+steroid) had no effect on the healing rate. As compared with control values, the peak scores for subepithelial haze were significantly lower in eyes that had received bFGF; the regression on time of the haze in the growth factor group paralleled that in eyes receiving continuous steroid treatment. These results demonstrate for the first time the efficiency of a growth factor in modulating the wound-healing response after excimer laser photoablation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Biphasic effect of the mitotoxin bFGF-saporin on bovine lens epithelial cell growth: effect of cell density and extracellular matrix.

We have studied the effect of a specific FGF receptor suicide antagonist on the growth of bovine epithelial cells (BEL cells) in culture. This basic fibroblast growth factor-saporin conjugate (bFGF-SAP) has a biphasic effect on bovine lens epithelial cells (BEL cells). Whereas 0.01 nM and 0.1 nM bFGF-SAP stimulate BEL cells proliferation, 1 nM and 10 nM bFGF-SAP have the predicted toxic effects on BEL cell growth. The toxicity of bFGF-SAP is observed 2 to 3 days after the initial treatment and depends on cell density. Accordingly, the sensitivity of confluent cells to bFGF-SAP is reduced compared to sparse cells. A time course analysis reveals that bFGF-SAP is effective after a short exposure to cells and that its effects are not increased with longer treatments. Cell growth on bFGF-SAP pretreated extracellular matrix (ECM) or posterior lens capsule (PLC) is also affected. Basic FGF-SAP has been shown to bind to the extracellular material, allowing a modulation of lens cells migration and survival by a single treatment in vitro. This finding raises the possibility of its use in vivo to prevent capsules invasion by lens cells after cataract surgery.

Animals

Analysis of regurgitant jets in natural and bio-prosthetic heart valves.

Artificial bio-prosthetic heart valves are prone to fatigue tearing, having a 50% failure rate in ten years. Tears in valves give rise to pulsing reverse flow back through the valve. This is termed regurgitant flow and the resultant jet of blood a regurgitant jet. The regurgitant volume of the jet during the pulsing cycle gives a measure of the severity of the valve defect and clinical significance. Hence, it is important for the cardiologists to be able to quantify this volume. Although the velocity of the regurgitant jet can be determined using Doppler ultrasound, the dimensions of the heart valve lesion cannot be measured directly; hence, the volumetric flow rate cannot be quantified accurately. At present the severity of the regurgitant jet is assessed qualitatively from the intrusion of the jet into the cardiac chamber. In the present study, classical mathematical theories of turbulent jets have been used to describe the velocity distributions for the types of jets expected in defective heart valves and these distributions have been verified experimentally. One of these models has been developed to enable the regurgitant volumetric flow through an axisymmetric orifice of unknown radius to be calculated from the velocity distribution of the jet. This relationship may be used in conjunction with ultrasound techniques to quantify the regurgitant volume within defective artificial heart valve implants. The present study shows that there is a significant difference in the velocity distributions in jets emanating from axisymmetric and high aspect ratio slots.(ABSTRACT TRUNCATED AT 250 WORDS)

Bioprosthesis

Images of 16S ribosomal RNA by scanning tunnelling microscopy.

We report the use of scanning tunnelling microscopy (STM) to study surface topographies of complex nucleic acid structures. From low-resolution STM images of uncoated 16S ribosomal RNA, we demonstrate the possibility of determining several objective parameters (molecular mass and radius of gyration) in order to characterize and identify the molecules observed. These parameters were compared with values obtained by other physical methods and the radius of gyration was found to be the most reliable. At high resolution, it was possible to measure the main dimensions of selected V-form particles more precisely than with electron microscopy. Images of the more compact form have been also obtained that show different domains in the macromolecular structure.

Escherichia coli

[Neuropsychological sequelae in children treated for brain tumor].

Treatment modalities of childhood brain tumors are associated with adverse neuropsychologic sequelae that may be manifested years after therapy. Based on recent published studies, the authors review the etiological factors, the symptoms and the evolutive features of these disorders and their management.

Brain Neoplasms

[Nanophthalmos with uveal effusion].

A typical case of nanophthalmos with uveal effusion syndrome is reported. Clinical, pathological and therapeutic aspects of uveal effusion syndrome are discussed. A surgical treatment consisting of lamellar sclerectomies is proposed.

Adult

Rheology of bovine bone marrow.

The viscosity of bovine bone marrow was measured using samples taken from proximal and distal sites of five radii. The viscosity was found to be independent of shear rate and temperature above 37 degrees C (distal samples) and 42 degrees C (proximal samples). The viscosity of all samples fell to a lower limit of 0.04 Pas above these temperatures, irrespective of the treatments used. Below them the measured viscosity of the proximal marrow was some ten times that of the distal marrow at 35 degrees C and some 15 times that of the distal marrow at 30 degrees C. Below 30 degrees C the proximal marrow solidified. Distal marrow remained liquid to below 20 degrees C.

Animals

[Orthopedic treatment of regular dorsal and dorsolumbar hyperkyphosis. New principles of active correction].

The orthopaedic treatment of hyper-kyphosis should not be unique. If the principles of treatment are different in relation with the thoracic or thoraco-lumbar localisation of the apex of the deformity, it is necessary to distinguish for the middle thoracic curve two types of patients: these in whom the kyphosis and the lordosis are balanced (the cast must diminish the lumbar lordosis and the imbalanced posterior types with a great kyphotic curve and a short compensatory lordosis which is important not to be diminish by the treatment. The principles of plaster casting are described in the two types; emphasizing on the unlucky aspect of the sternal support in the middle thoracic kyphosis and in the necessity of the thoracic modification if we wish to obtain a good result. The active expiratory reeducation is capital before and during the treatment.

Casts, Surgical